title: Association of systemic and intra-articular osteoclastogenic potential, pro-inflammatory mediators and disease activity with the form of inflammatory arthritis.
abstract: OBJECTIVE
  We aimed to assess osteoclastogenic potential of peripheral blood mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in different forms of arthritis and to correlate it with inflammatory mediators within intra-articular and circulatory compartments.
  
  
  METHODS
  Paired PBMC and SFMC samples of patients with rheumatoid arthritis (RA; n = 10) and psoriatic arthritis (PsA; n = 10), and PBMC of healthy controls were cultured to assess osteoclastogenic potential by the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor activator of nuclear factor-κΒ (RANK), cFMS, and TRAP). Osteoclastogenesis was correlated with the arthritis-related inflammatory indicators in serum and synovial fluid (SF).
  
  
  RESULTS
  Number of OCs differentiated from PBMC was significantly higher in RA and PsA compared with control, with RA having more OCs compared with PsA. There was no difference in SFMC OC number between arthritic patients, but RANK expression in OCs differentiated from SFMC was higher in PsA compared with RA. SF of PsA patients more potently induced OC differentiation from control CD3(-)CD19(-)CD56(-)CD11b(+)CD115(+) PBMC compared with RA, paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC gene expression of interleukin-18 and Fas-ligand were observed.
  
  
  CONCLUSIONS
  Osteoclastogenic potential is systemically enhanced in patients with RA, paralleled by disordered systemic and local expression of proinflammatory mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our study reveals arthritis-specific mediators associated with the form of arthritis, indicating clinical relevance for diagnosis and treatment.
authors.affiliation: Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Salata 12, Zagreb, 10000, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Ikić
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Jajić
authors.forename: Elvira
authors.initials: E
authors.lastname: Lazić
authors.forename: Sanja
authors.initials: S
authors.lastname: Ivčević
authors.forename: Frane
authors.initials: F
authors.lastname: Grubišić
authors.forename: Ana
authors.initials: A
authors.lastname: Marušić
authors.forename: Nataša
authors.initials: N
authors.lastname: Kovačić
authors.forename: Danka
authors.initials: D
authors.lastname: Grčević
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000166:cytology* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase